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https://www.readbyqxmd.com/read/28904869/high-glucose-stimulates-expression-of-aldosterone-synthase-cyp11b2-and-secretion-of-aldosterone-in-human-adrenal-cells
#1
Hiroki Shimada, Naotaka Kogure, Erika Noro, Masataka Kudo, Kaori Sugawara, Ikuko Sato, Kyoko Shimizu, Makoto Kobayashi, Dai Suzuki, Rehana Parvin, Takako Saito-Ito, Akira Uruno, Akiko Saito-Hakoda, William E Rainey, Sadayoshi Ito, Atsushi Yokoyama, Akira Sugawara
Aldosterone synthase is the key rate-limiting enzyme in adrenal aldosterone production, and induction of its gene (CYP11B2) results in the progression of hypertension. As hypertension is a frequent complication among patients with diabetes, we set out to elucidate the link between diabetes mellitus and hypertension. We examined the effects of high glucose on CYP11B2 expression and aldosterone production using human adrenal H295R cells and a stable H295R cell line expressing a CYP11B2 5'-flanking region/luciferase cDNA chimeric construct...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28878618/the-non-survival-effects-of-glial-cell-line-derived-neurotrophic-factor-on-neural-cells
#2
REVIEW
Daniel Cortés, Oscar A Carballo-Molina, María José Castellanos-Montiel, Iván Velasco
Glial cell line-derived neurotrophic factor (GDNF) was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs). Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neurite outgrowth and other phenomena that have been less studied than survival and are now more extendedly described here in this review article. During development, GDNF favors the commitment of neural precursors towards dopaminergic, motor, enteric and adrenal neurons; in addition, it enhances the axonal growth of some of these neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28844658/direct-reprogramming-of-resident-ng2-glia-into-neurons-with-properties-of-fast-spiking-parvalbumin-containing-interneurons
#3
Maria Pereira, Marcella Birtele, Shelby Shrigley, Julio Aguila Benitez, Eva Hedlund, Malin Parmar, Daniella Rylander Ottosson
Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. Here, we show that neurons reprogrammed using Ascl1, Lmx1a, and Nurr1 functionally mature and integrate into existing brain circuitry and that the majority of the reprogrammed neurons have properties of fast-spiking, parvalbumin-containing interneurons...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28800627/suppressive-effects-of-rxr-agonist-pa024-on-adrenal-cyp11b2-expression-aldosterone-secretion-and-blood-pressure
#4
Dai Suzuki, Akiko Saito-Hakoda, Ryo Ito, Kyoko Shimizu, Rehana Parvin, Hiroki Shimada, Erika Noro, Susumu Suzuki, Ikuma Fujiwara, Hiroyuki Kagechika, William E Rainey, Shigeo Kure, Sadayoshi Ito, Atsushi Yokoyama, Akira Sugawara
The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells...
2017: PloS One
https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#5
Willemieke M Kouwenhoven, Lars von Oerthel, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#6
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28769982/nurr1-downregulation-favors-osteoblastic-differentiation-of-mscs
#7
Adriana Di Benedetto, Francesca Posa, Claudia Carbone, Stefania Cantore, Giacomina Brunetti, Matteo Centonze, Maria Grano, Lorenzo Lo Muzio, Elisabetta A Cavalcanti-Adam, Giorgio Mori
Mesenchymal stem cells (MSCs) have been identified in human dental tissues. Dental pulp stem cells (DPSCs) were classified within MSC family, are multipotent, can be isolated from adult teeth, and have been shown to differentiate, under particular conditions, into various cell types including osteoblasts. In this work, we investigated how the differentiation process of DPSCs toward osteoblasts is controlled. Recent literature data attributed to the nuclear receptor related 1 (NURR1), a still unclarified role in osteoblast differentiation, while NURR1 is primarily involved in dopaminergic neuron differentiation and activity...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28746897/parkinsonian-features-in-aging-gfap-hmox1-transgenic-mice-overexpressing-human-ho-1-in-the-astroglial-compartment
#8
Wei Song, Marisa Cressatti, Hillel Zukor, Adrienne Liberman, Carmela Galindez, Hyman M Schipper
Epigenetic influences mediating brain iron deposition, oxidative mitochondrial injury, and macroautophagy in Parkinson disease and related conditions remain enigmatic. Here, we show that selective overexpression of the stress protein, heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age results in nigrostriatal hypodopaminergia associated with locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase, DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of α-synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and reelin)...
June 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28743636/valproate-increases-dopamine-transporter-expression-through-histone-acetylation-and-enhanced-promoter-binding-of-nurr1
#9
Ashley L Green, Le Zhan, Aseel Eid, Helmut Zarbl, Grace L Guo, Jason R Richardson
The dopamine transporter (DAT) is the key regulator of dopaminergic transmission and is a target of several xenobiotics, including pesticides and pharmacological agents. Previously, we identified a prominent role for histone deacetylases in the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50% increase in protein levels, which were accompanied by increased H3 acetylation levels...
October 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28705346/efficient-generation-of-dopamine-neurons-by-synthetic-transcription-factor-mrnas
#10
Sang-Mi Kim, Mi-Sun Lim, Eun-Hye Lee, Sung Jun Jung, Hee Yong Chung, Chun-Hyung Kim, Chang-Hwan Park
Generation of functional dopamine (DA) neurons is an essential step for the development of effective cell therapy for Parkinson's disease (PD). The generation of DA neurons can be accomplished by overexpression of DA-inducible genes using virus- or DNA-based gene delivery methods. However, these gene delivery methods often cause chromosomal anomalies. In contrast, mRNA-based gene delivery avoids this problem and therefore is considered safe to use in the development of cell-based therapy. Thus, we used mRNA-based gene delivery method to generate safe DA neurons...
September 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28691794/ligand-dependent-switch-from-rxr-homo-to-rxr-nurr1-heterodimerization
#11
Marcel Scheepstra, Sebastian A Andrei, Rens M J M de Vries, Femke A Meijer, Jian-Nong Ma, Ethan S Burstein, Roger Olsson, Christian Ottmann, Lech-Gustav Milroy, Luc Brunsveld
Retinoid X receptors (RXRs) play key roles in many physiological processes in both the periphery and central nervous system. In addition, RXRs form heterodimers with other nuclear receptors to exert their physiological effects. The nuclear receptor related 1 protein (NURR1) is particularly interesting because of its role in promoting differentiation and survival of dopamine neurons. However, only a small number of RXR-heterodimer selective modulators are available, with limited chemical diversity. This work describes the synthesis, biochemical evaluation, and structural elucidation of a novel series of RXR ligands with strongly biased interactions with RXRα-NURR1 heterodimers...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28685937/neuroimmunomodulatory-properties-of-dpscs-in-an-in-vitro-model-of-parkinson-s-disease
#12
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Vasudevan Mani, Noor Hayaty Abu Kasim
In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons...
September 2017: IUBMB Life
https://www.readbyqxmd.com/read/28607093/prostaglandin-e2-is-essential-for-efficacious-skeletal-muscle-stem-cell-function-augmenting-regeneration-and-strength
#13
Andrew T V Ho, Adelaida R Palla, Matthew R Blake, Nora D Yucel, Yu Xin Wang, Klas E G Magnusson, Colin A Holbrook, Peggy E Kraft, Scott L Delp, Helen M Blau
Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC expansion. An acute treatment with PGE2 suffices to robustly augment muscle regeneration by either endogenous or transplanted MuSCs...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28585189/modulatory-role-of-nurr1-activation-and-thrombin-inhibition-in-the-neuroprotective-effects-of-dabigatran-etexilate-in-rotenone-induced-parkinson-s-disease-in-rats
#14
Esraa A Kandil, Rabab H Sayed, Lamiaa A Ahmed, Mai A Abd El Fattah, Bahia M El-Sayeh
Recently, it has been shown that both decreased nuclear receptor-related 1 (Nurr1) expression and thrombin accumulation are involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). The new anticoagulant dabigatran etexilate (DE) is a direct thrombin inhibitor that owns benzimidazole group, which has been proposed to activate Nurr1. In the present study, we examined the neuroprotective effects of DE in rotenone model of PD. Rotenone was injected subcutaneously at a dose of 1.5 mg/kg every other day for 21 days...
June 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28569795/cystatin-c-as-a-potential-therapeutic-mediator-against-parkinson-s-disease-via-vegf-induced-angiogenesis-and-enhanced-neuronal-autophagy-in-neurovascular-units
#15
Jing Zou, Zhaoyu Chen, Xiaobo Wei, Zhigang Chen, Yongmei Fu, Xiaoyan Yang, Dan Chen, Rui Wang, Peter Jenner, Jia-Hong Lu, Min Li, Zhuohua Zhang, Beisha Tang, Kunlin Jin, Qing Wang
Cystatin C (CYS C, Cst3) is an endogenous cysteine protease inhibitor that plays neuroprotective roles in neurodegenerative diseases. We aimed to explore the association of CYS C with Parkinson's disease (PD) models and investigate its involvement in the role of neurovascular units (NVUs) in PD neuro-pathogenesis. We used A53T α-synuclein (SNCA) transgenic mice and 6-hydroxydopamine-lesioned DAergic PC12 cells as experimental PD models to investigate the mechanisms behind this association. The injections of CYS C were administered to the right substantia nigra (SN) of A53T SNCA transgenic mice to measure the effects of CYS C in transgenic A53T SNCA mice...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28533388/selective-lowering-of-synapsins-induced-by-oligomeric-%C3%AE-synuclein-exacerbates-memory-deficits
#16
Megan E Larson, Susan J Greimel, Fatou Amar, Michael LaCroix, Gabriel Boyle, Mathew A Sherman, Hallie Schley, Camille Miel, Julie A Schneider, Rakez Kayed, Fabio Benfenati, Michael K Lee, David A Bennett, Sylvain E Lesné
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28466092/repeated-social-defeat-and-the-rewarding-effects-of-cocaine-in-adult-and-adolescent-mice-dopamine-transcription-factors-probdnf-signaling-pathways-and-the-trkb-receptor-in-the-mesolimbic-system
#17
Sandra Montagud-Romero, Cristina Nuñez, M Carmen Blanco-Gandia, Elena Martínez-Laorden, María A Aguilar, Javier Navarro-Zaragoza, Pilar Almela, Maria-Victoria Milanés, María-Luisa Laorden, José Miñarro, Marta Rodríguez-Arias
RATIONALE: Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. OBJECTIVE: The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice...
July 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28452458/chiro-optical-modulation-for-nurr1-production-from-stem-cells
#18
Madhumita Patel, Hyo Jung Moon, Ja Hye Hong, Byeongmoon Jeong
Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of dopaminergic neurons in adult midbrain of which deficiency leads to Parkinson's disease. To enhance the NURR1 production of neural cells, various approaches are under investigation. Here we report that NURR1 is highly expressed in stem cells by exposure to an L-polarized blue light emitting diode (LED). Compared to stem cells cultured in the absence of a LED, under polarized green and red LEDs, the stem cells exposed to a polarized blue LED significantly enhanced neuronal biomarkers such as neurofilament M (NFM) and neuron specific enolase (NSE) at both mRNA and protein levels...
May 2, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28419831/molecular-phenotyping-of-transient-postnatal-tyrosine-hydroxylase-neurons-in-the-rat-bed-nucleus-of-the-stria-terminalis
#19
David A Carter
The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype...
April 15, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28365874/developmental-vitamin-d-dvd-deficiency-reduces-nurr1-and-th-expression-in-post-mitotic-dopamine-neurons-in-rat-mesencephalon
#20
Wei Luan, Luke Alexander Hammond, Edmund Cotter, Geoffrey William Osborne, Suzanne Adele Alexander, Virginia Nink, Xiaoying Cui, Darryl Walter Eyles
Developmental vitamin D (DVD) deficiency has been proposed as an important risk factor for schizophrenia. Our previous study using Sprague Dawley rats found that DVD deficiency disrupted the ontogeny of mesencephalic dopamine neurons by decreasing the mRNA level of a crucial differentiation factor of dopamine cells, the nuclear receptor related 1 protein (Nurr1). However, it remains unknown whether this reflects a reduction in dopamine cell number or in Nurr1 expression. It is also unclear if any particular subset of developing dopamine neurons in the mesencephalon is selectively affected...
April 1, 2017: Molecular Neurobiology
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